Davos 2011 - Device therapy in heartfailure Update of the ...assets.escardio.org/assets/Presentations/OTHER2011/Davos/Swedb… · CRT-P/CRT-D* is recommended to reduce morbidity and

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Device therapy in heartfailure

Update of the ESC guidelines

Professor of Medicine

Department of emergency and cardiovascular medicine

Sahlgrenska Academy

University of Gothenburg, Sweden

[email protected]

Karl Swedberg

Disclosure

No conflicts in relation to this presentation

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2010 Focused Update of ESC Guidelines on

Device Therapy in Heart Failure

An Update of the 2008 ESC guidelines for the Diagnosis and Treatment of Acute and Chronic

Heart Failure and the 2007 ESC guidelines for Cardiac and Resynchronization Therapy,

developed in collaboration with the HFA and EHRA

Authors/Task Force Members: Kenneth Dickstein* (Chairperson) (Norway), Panos E. Vardas** (Chairperson) (Greece),

Angelo Auricchio (Switzerland), Jean-Claude Daubert (France), Cecilia Linde (Sweden), John McMurray (UK), Piotr

Ponikowski (Poland), Silvia Giuliana Priori (Italy), Richard Sutton (UK), Dirk van Veldhuisen (Netherlands)

ESC Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson) (France), Angelo Auricchio (Switzerland),

Jeroen Bax (The Netherlands), Claudio Ceconi (Italy), Veronica Dean (France), Gerasimos Filippatos (Greece), Christian

Funck-Brentano (France), Richard Hobbs (UK), Peter Kearney (Ireland), Theresa McDonagh (UK), Bogdan A. Popescu

(Romania), Zeljko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Panos

Vardas (Greece), Petr Widimsky (Czech Republic)

Document Reviewers, Michal Tendera (CPG Review Coordinator) (Poland), Stefan D. Anker (Germany), Jean-Jacques

Blanc (France), Maurizio Gasparini (Italy), Arno W. Hoes (Netherlands), Carsten W. Israel (Germany), Zbigniew Kalarus

(Poland), Bela Merkely (Hungary), Karl Swedberg (Sweden), A. John Camm (UK)

European Heart Journal

doi:10.1093/eurheartj/ehq337

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Classes of Recommendations

DefinitionSuggested wording

to useClass I Evidence and/or general

agreement that a given treatment or procedure is beneficial, useful, effective.

Is recommended/is indicated

Class II Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure.

Class IIa Weight of evidence/opinion is in favour of usefulness/efficacy.

Should be considered

Class IIb Usefulness/efficacy is less well established by evidence/opinion.

May be considered

Class III Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful.

Is not recommended



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LEVELS OF EVIDENCE



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Evidence table 1: Inclusion criteria in RCTs evaluating CRT in heart failure

Trial Patients NYHA

class

LVEF(%) LVEDD (mm) SR/AF QRS

(ms)

ICD

MUSTIC-SR (16) 58 III 35% 60 SR 150 No

MIRACLE (5) 453 III,IV 35% 55 SR 130 No

MUSTIC AF (35) 43 III 35% 60 AF 200 No

PATH CHF (6) 41 III,IV 35% NA SR 120 No

MIRACLE ICD (8) 369 III,IV 35% 55 SR 130 Yes

CONTAK CD (55) 227 II,IV 35% NA SR 120 Yes

MIRACLE ICD II (9) 186 II 35% 55 SR 130 Yes

PATH CHF II (56) 89 III,IV 35% NA SR 120 Yes/No

COMPANION (10) 1520 III,IV 35% NA SR 120 Yes/No

CARE HF (11) 814 III,IV 35% 30 SR 120 No


REVERSE (21, 22) 610 I,II <40% 55 SR >120 Yes/No

MADIT CRT (20) 1800 I,II <30% NA SR >130 ms Yes



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CARE-HF

Mortality or CV hospitalisation

Cleland et al. N Engl J Med 2005;352:1539-49

RRR=52%

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Recommendation in patients with heart failure

in NYHA function class III/IV

Recommendation Patient Population Class LoE

CRT-P/CRT-D* is

recommended to

reduce morbidity and

mortality

NYHA function class III/IV

LVEF≤35%, QRS≥120 ms, SR

Optimal medical therapy

Class IV patients should be

ambulatory**

I A

*Reasonable expectation of survival with good functional status for >1 year for CRT-D.

Patients with a secondary prevention indication for an ICD should receive a CRT-D.

** No admissions for HF during the last month and a reasonable expectation of survival >6 months.



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Key points:

• New: LV dilatation no longer required

• New: Class IV patients should be ambulatory

• New: Reasonable expectation of survival with good

functional status for >1 year for CRT-D

• Evidence is strongest for patients with typical LBBB

• Similar level of evidence for CRT-P and CRT-D

CRT-P/CRT-D in patients with heart failure

in NYHA function class III/IV



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Number at Risk

CRT OFF 82 79 76 70 39

CRT ON 180 176 173 168 77

Daubert et al. JACC 2009;54:1837-1846

REVERSE 24-months analysis:Reductions in risk of first HF hospitalisation or death

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24Months Since Randomisation

Perc

enta

ge H

ospitalis

ed for

HF

or

Die

d

CRT ON

CRT OFF

24.0%

11.7%

Hazard Ratio: 0.38

95%CI: 0.20-0.73

P=0.003

RRR=62%

www.escardio.org N Engl J Med 2009;361

Probability of Survival Free of Heart Failure

MADIT-CRT

RRR=34%

www.escardio.org Moss et al. N Engl J Med 2009;361:1329-38

MADIT-CRT: Risk of death or heart failure

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Recommendation in patients with heart failure

in NYHA function class II

Recommendation Patient Population Class Level

CRT preferentially by

CRT-D is recommended

to reduce morbidity

or to prevent disease

progression*

NYHA function class II



I A

* The guideline indication has been restricted to patients with HF in NYHA

function class II with a QRS width ≥150 ms, a population with a high likelihood

of a favourable response.



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CRT-D in patients with heart failure

in NYHA function class I/II

Key points:

• 2 recent, randomised, prospective, multicentre trials in mild HF

(MADIT-CRT and REVERSE) demonstrate reduced morbidity

• 18% of patients in REVERSE and 15% of patients in MADIT-CRT

were in NYHA I class at baseline

• Improvement primarily seen in patients with QRS≥150 ms and/or

typical LBBB

• Women with LBBB showed a particularly favourable response

• Survival advantage not established

• In MADIT-CRT the extent of reverse remodelling was concordant

with and predictive of improvement in clinical outcomes



RAFT

RAFTCRT/ICD in mild-moderate symptoms

Tang et al NEJM 2010

www.escardio.org Ferreira et al. Europace 2008;10:809-815

HF hospitalisation / 1 yearAV ablation vs. AF drugs

AtrialFibrillation

www.escardio.orgGasparini et al. Eur Heart J 2008;29:1644-1652

Comparison of CRT in sinusrythm (n=1042), AF with AV

ablation (n=118) vs. AF drug (n=125) therapy

Adjusted hazard ratios for death

AtrialFibrillation

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Recommendations in patients with heart failure

and permanent atrial fibrillation

Recommendations Patient Population Class Level

CRT-P/CRT-D* should be

considered to reduce

morbidity


LVEF≤35%, QRS≥130 ms

Pacemaker dependency

induced by AV nodal

ablation

IIa B



morbidity



Slow ventricular rate and

frequent pacing**

IIa C

*Reasonable expectation of survival with good functional status for >1 year for CRT-D.

Patients with a secondary prevention indication for an ICD should receive a CRT-D.

** Frequent pacing is defined as ≥95% pacemaker dependency



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and permanent atrial fibrillation

Key points:

• Approximately 1/5 of CRT implantations in Europe are in

patients with permanent AF

• NYHA class III/IV symptoms and an LVEF ≤35% are

well-established indications for ICD

• Frequent pacing is defined as ≥95% pacemaker dependency

• AV nodal ablation may be required to assure adequate pacing

• Evidence strongest for patients with an LBBB pattern

• Insufficient evidence for mortality recommendation



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Recommendations in patients with heart failure

and a concomitant class I pacemaker indication


CRT-P/CRT-D* is

recommended to reduce

morbidity


LVEF≤35%, QRS ≥120 msI B



morbidity


LVEF≤35%, QRS<120 msIIa C

CRT-P/CRT-D* may be


morbidity

NYHA function class II

LVEF≤35%, QRS<120 msIIb C

* Reasonable expectation of survival with good functional status for >1

year for CRT-D. Patients with a secondary prevention indication for an

ICD should receive a CRT-D.



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and a conventional pacemaker indication

Key points:

•In patients with a conventional indication for pacing, NYHA III/IV

symptoms, LVEF ≤35%, QRS width ≥120 ms, a CRT-P/CRT-D is indicated

•RV pacing will induce dyssynchrony

•Chronic RV pacing in patients with LV dysfunction should be avoided

•CRT may permit adequate uptitration of beta-blocker treatment



www.escardio.orgSlaughter et al. N Engl J Med 2009;361:2241-51

HEARTMATE Survival

n=192

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Recommendation in patients with

severe heart failure ineligible for transplant


LVAD may be considered

as destination treatment

to reduce mortality

NYHA function class IIIB/IV

LVEF≤25%

peak VO2<14 ml/kg/min*

IIb B

*If obtainable



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Left Ventricular Assist Device as destination therapy for

patients with severe HF ineligible for cardiac transplantation

Key points:

• The NIH INTERMACS registry indicates that ~10% of

patients in clinical practice receive an LVAD as destination therapy

• Patient population mainly consists of patients on inotropic (and/or

mechanical) support prior to LVAD implantation

• Patient selection is crucial and candidates should not have significant

renal, pulmonary or hepatic dysfunction or infection

• The available evidence suggests that a continuous flow device is

superior to a pulsatile flow device

• No controlled data available as bridge to heart transplantation



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Gaps in evidenceCRT in Patients with Heart Failure

Selection criteria CRT Implantation Issues

• Chronological/biological age?

• Major Comorbidities?

• QRS between 120-130 ms?

• RBBB?

• LVEF >35%?

• Role of imaging to detect volumes/

mechanical dyssynchrony/viable

myocardium

• Mitral insufficiency?

• NYHA function class I?

• CRT-P or CRT-D?

• Importance of operator experience?

• Role of imaging to determine optimal lead

placement?

• Skills in optimal AV, VV programming?

• Which factors in patient selection, lead

placement or follow-up predict a

poor response?

• Health resource utilisation and cost/benefit

ratio?

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CRT-P/CRT-D* is recommended

to reduce morbidity and

mortality

NYHA class III/IV symptoms



Class IV patients should be ambulatory**

I A

CRT preferentially by CRT-D* is

recommended to reduce

morbidity or to prevent disease

progression

NYHA class II symptoms

LVEF≤35%, QRS≥150 ms, SRI A


considered to reduce morbidity

Permanent Atrial Fibrillation

NYHA class III/IV


Pacemaker dependency induced by AV nodal ablation

IIa B



Permanent Atrial Fibrillation

NYHA class III/IV


Slow ventricular rate and frequent pacing***

IIa C

Summary of indications for CRT in patients with heart failure

CRT-P/CRT-D* is recommended

to reduce morbidity

Class I indication for pacemaker

NYHA class III/IV

LVEF≤35%, QRS ≥120 ms

I B




NYHA class III/IV

LVEF≤35%, QRS<120 ms

IIa C

CRT-P/CRT-D* may be



NYHA class II

LVEF≤35%, QRS<120 ms

IIb C

Patient populationRecommendations CoR LoE

LVAD may be considered as

destination treatment to reduce

mortality

NYHA IIIB/IV symptoms

Ineligible for cardiac transplantation

LVEF≤25%

IIb B

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●BACKUP

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Evidence table 1: Inclusion criteria in RCTs evaluating CRT in heart failure

Trial Patients NYHA

class

LVEF(%) LVEDD (mm) SR/AF QRS

(ms)

ICD

MUSTIC-SR (16) 58 III 35% 60 SR 150 No

MIRACLE (5) 453 III,IV 35% 55 SR 130 No

MUSTIC AF (35) 43 III 35% 60 AF 200 No

PATH CHF (6) 41 III,IV 35% NA SR 120 No

MIRACLE ICD (8) 369 III,IV 35% 55 SR 130 Yes

CONTAK CD (55) 227 II,IV 35% NA SR 120 Yes

MIRACLE ICD II (9) 186 II 35% 55 SR 130 Yes

PATH CHF II (56) 89 III,IV 35% NA SR 120 Yes/No

COMPANION (10) 1520 III,IV 35% NA SR 120 Yes/No



REVERSE (21, 22) 610 I,II <40% 55 SR >120 Yes/No

MADIT CRT (20) 1800 I,II <30% NA SR >130 ms Yes

RAFT (57) 1800

Canada

II,III <30% >60 SR/AF >130

200 *

Yes



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Trial Endpoints Design Main findings

MUSTIC-SR (16) 6MWT, QoL, pVO2, Hosp Single-blinded, controlled, crossover, 6 months CRT-P improved: 6MWT, QOL, pVO2; reduced Hosp

MIRACLE (8) NYHA class, QoL, pVO2 Double-blinded, controlled, 6 months CRT-P improved: NYHA, pVO2, 6MWT

MUSTIC AF (35) 6MWT, QoL, pVO2, Hosp Single-blinded, controlled, crossover, 6 months CRT-P improved all; reduction of Hosp

PATH CHF (6) 6MWT, pVO2 Single-blinded, controlled, crossover, 12 months CRT-P improved: 6MWT; pVO2

MIRACLE ICD (8) 6MWT, QoL, Hosp Double-blinded, ICD vs. CRT-D 6 months CRT-D improved all from baseline (not ICD)

CONTAK CD (54)All-cause death + HF Hosp, pVO2,

6MWT, NYHA class, QoL, LVEDD,

LVEF

Double-blinded, ICD vs. CRT-D 6 monthsCRT-D improved: pVO2, 6MWT; reduced LVEDD

and increased LVEF

MIRACLE ICD II (9)VE/CO2, pVO2, NYHA, QoL,

6MWT, LV volumes, LVEF Double-blinded, ICD vs. CRT-D 6 months CRT-D improved: NYHA, VE/CO2; volumes, LVEF

COMPANION (10) (1) All-cause death or HospDouble-blinded, controlled, OPT, CRT-D, CRT-P,

about 15 months

CRT-P/CRT-D: reduced (1)

CARE-HF (11)(1) All-cause death or CV event

(2) All-cause death Double-blinded, controlled, OPT, CRT-P, 29 months CRT-P reduced (1) and (2)

REVERSE (21)(1) % worsened by clinical

composite endpoint, (2) LVESVi,

(3) HF hosp, (4) all-cause death

Double-blinded, controlled, OPT, CRT-P +ICD, 12months Primary endpoint NS

CRT-P/CRT-D reduced (2) and (3) hosp but not (4)

MADIT–CRT (20)(1) HFevent or death

(2) All-cause death

(3) LVESV

Controlled, CRTP, CRT-D, 2.4 years CRT-D reduced (1) and (3c) but not (2)

Evidence table 2: Endpoints, design and main findings of the

RCTs evaluating CRT in heart failure



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-35 -30 -25 -20 -15 -10 -5 0

0

2

4

6

8

10

12

14

ICD QuartilesCRT-D Quartiles

Pri

ma

ry E

ve

nt

Ra

te a

fte

r 1

ye

ar

(pe

r 1

00

-pe

rso

n y

ea

rs)

Percent Change in LV End Diastolic Volume, Baseline to 12-months

Concordance with Outcomes

Solomon et al Circ 2010 10.1161/CIRCULATIONAHA.110.955039

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Traditionally, guideline recommendations are based on the

outcomes in the cohort of patients described by the inclusion

criteria in the protocols of Randomised Clinical Trials.

In contrast to previous guidelines, this focused update considers

the characteristics of the patients included in the trials and

contains several examples.

The text accompanying these recommendations explains and

justifies the decisions to diverge from a traditional

recommendation based strictly on the protocol inclusion criteria.

The task force hopes that the users of the Guidelines will

appreciate that this adjustment provides a more realistic

application of the trial evidence to daily clinical practice.

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Monitoring of MADIT CRT by the DSMB

N Engl J Med 2009;361

_______

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In MADIT-CRT, although the protocol permitted inclusion

of patients in both NYHA I and II function class, only 15%

of the patients included in this trial were classified as

NYHA I, many of whom had been previously symptomatic.

Similarly, although the inclusion criteria permitted

randomisation of patients with a QRS width ≥130 m, the

favourable effect on the primary endpoint was limited to

patients with a QRS width ≥150 ms, a prospective, pre-

specified cut-off.

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In patients with mild symptoms and a QRS width of 120-150 ms, clinicians may wish to assess other criteria associated with a favourable outcome such as:

•dyssynchrony by echocardiography•LV dilatation•LBBB•non-ischaemic cardiomyopathy•recent NYHA class III symptoms

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ESC CRT SURVEY

NYHA I 2%

NYHA II 20%

Age ≥ 75 (%) 31%

Atrial fibrillation 23%

QRS duration < 120 ms 9%

QRS duration 120 – 129 ms 10%

Eur Heart J 2009;30:2450–2460

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Parachutes appear to reduce the risk of injury, but their effectiveness has not been proved with randomised controlled trials

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Davos 2011 - Device therapy in heartfailure Update of the ...assets.escardio.org/assets/Presentations/OTHER2011/Davos/Swedb… · CRT-P/CRT-D* is recommended to reduce morbidity and